Predicting Protein Ligand Binding Sites by Combining Evolutionary Sequence Conservation and 3D Structure
Figure 3
Comparison of the binding site predictions of Structure and ConCavity on three example proteins.
The three proteins presented here correspond to those shown in Figure 2. In each pane, ligand binding residue scores have been mapped to the protein surface. Warmer colors indicate a higher binding score. Pocket predictions are shown as green meshes. (A) PDB: 3CWK. Both methods identify the binding site, but by considering conservation information (Figure 2A), ConCavity more accurately traces the ligand. (B) PDB: 2CWH. Structure significantly overpredicts the extent of the ligand in the bottom left corner as well as predicting an additional pocket on the reverse of the protein. ConCavity predicts only the two ligand binding pockets. (C) PDB: 1G6C. In order to visualize the predictions more clearly, only the secondary structure diagram of the protein is shown. This example illustrates the difficulty presented by multichain proteins; there are many cavities in the structure, but not all bind ligands. Structure identifies some of the relevant pockets, but focuses on the large, non-binding central cavity formed between the chains. Referring to this protein's conservation profile (Figure 2C), we see that the ligand binding pockets exhibit high conservation while the non-binding pockets do not. As a result, ConCavity selects only the relevant binding pockets. In each example, ConCavity selects the binding pocket(s) out of all potential pockets and more accurately traces the ligands' locations in these pockets.